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Astrocyte Pannexin 1 Suppresses LPS-Induced Inflammatory Responses to Protect Neuronal SH-SY5Y Cells.
Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2021-08-12 , DOI: 10.3389/fncel.2021.710820
Zhuo-Min Ling 1, 2 , Qian Wang 1 , Yu Ma 1 , Peng Xue 2 , Yun Gu 1 , Mao-Hong Cao 2, 3 , Zhong-Ya Wei 1
Affiliation  

Reactive astrogliosis is a key hallmark of inflammatory responses in the pathogenesis of brain injury, including Parkinson's disease (PD), but its role and regulatory mechanisms are not fully understood. Pannexin 1 (Panx 1) is a membrane channel that mediates substance release in many neurodegenerative diseases. However, the role of astrocyte Panx 1 in the regulation of PD-like neuroinflammation remains elusive. Here, we characterized the expression of Panx 1 in isolated primary astrocytes and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. The functions of Panx 1 in inflammatory cytokines expression and the viability of neuronal SH-SY5Y cells were examined in cultured cells treated with lipopolysaccharide (LPS) and 1-methyl-4-phenylpyridinium (MPP+). We found that Panx 1 expression was significantly increased under both LPS- and MPP+-treated conditions. Panx 1 downregulation suppressed LPS-induced pro-inflammatory cytokine expression but did not significantly affect MPP+-induced astrocyte apoptosis or inflammatory cytokine expression through treatment with the Panx 1 inhibitor carbenoxolone (CBX) and Panx 1 siRNA. Moreover, silencing Panx 1 in reactive astrocytes had a potentially protective effect on the viability of neuronal SH-SY5Y cells. Therefore, we propose that Panx 1 may serve as a key regulator in reactive astrocytes to intervene in the inflammatory response and maintain neuronal viability in the context of PD-like conditions.

中文翻译:

星形胶质细胞 Pannexin 1 抑制 LPS 诱导的炎症反应以保护神经元 SH-SY5Y 细胞。

反应性星形胶质细胞增生是包括帕金森病 (PD) 在内的脑损伤发病机制中炎症反应的关键标志,但其作用和调节机制尚不完全清楚。Pannexin 1 (Panx 1) 是一种膜通道,可在许多神经退行性疾病中介导物质释放。然而,星形胶质细胞 Panx 1 在 PD 样神经炎症调节中的作用仍然难以捉摸。在这里,我们表征了 Panx 1 在分离的原代星形胶质细胞和 1-methyl-4-phenyl-1,2,3,6-四氢吡啶 (MPTP) 诱导的 PD 模型中的表达。在用脂多糖 (LPS) 和 1-甲基-4-苯基吡啶 (MPP+) 处理的培养细胞中检查了 Panx 1 在炎性细胞因子表达中的功能和神经元 SH-SY5Y 细胞的活力。我们发现在 LPS 和 MPP+ 处理的条件下,Panx 1 表达显着增加。Panx 1 下调抑制了 LPS 诱导的促炎细胞因子表达,但通过使用 Panx 1 抑制剂卡苯氧酮 (CBX) 和 Panx 1 siRNA 治疗,并未显着影响 MPP+ 诱导的星形胶质细胞凋亡或炎性细胞因子表达。此外,在反应性星形胶质细胞中沉默 Panx 1 对神经元 SH-SY5Y 细胞的活力具有潜在的保护作用。因此,我们建议 Panx 1 可以作为反应性星形胶质细胞的关键调节剂,在 PD 样条件下干预炎症反应并维持神经元活力。Panx 1 下调抑制了 LPS 诱导的促炎细胞因子表达,但通过使用 Panx 1 抑制剂卡苯氧酮 (CBX) 和 Panx 1 siRNA 治疗,并未显着影响 MPP+ 诱导的星形胶质细胞凋亡或炎性细胞因子表达。此外,在反应性星形胶质细胞中沉默 Panx 1 对神经元 SH-SY5Y 细胞的活力具有潜在的保护作用。因此,我们建议 Panx 1 可以作为反应性星形胶质细胞的关键调节剂,在 PD 样条件下干预炎症反应并维持神经元活力。Panx 1 下调抑制了 LPS 诱导的促炎细胞因子表达,但通过使用 Panx 1 抑制剂卡苯氧酮 (CBX) 和 Panx 1 siRNA 治疗,并未显着影响 MPP+ 诱导的星形胶质细胞凋亡或炎性细胞因子表达。此外,在反应性星形胶质细胞中沉默 Panx 1 对神经元 SH-SY5Y 细胞的活力具有潜在的保护作用。因此,我们建议 Panx 1 可以作为反应性星形胶质细胞的关键调节剂,在 PD 样条件下干预炎症反应并维持神经元活力。在反应性星形胶质细胞中沉默 Panx 1 对神经元 SH-SY5Y 细胞的活力具有潜在的保护作用。因此,我们建议 Panx 1 可以作为反应性星形胶质细胞的关键调节剂,在 PD 样条件下干预炎症反应并维持神经元活力。在反应性星形胶质细胞中沉默 Panx 1 对神经元 SH-SY5Y 细胞的活力具有潜在的保护作用。因此,我们建议 Panx 1 可以作为反应性星形胶质细胞的关键调节剂,在 PD 样条件下干预炎症反应并维持神经元活力。
更新日期:2021-08-12
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